Anh Do Duc, The Nguyen Trong, Song Le Huu, Mueller Anja, Velavan Thirumalaisamy P, Seliger Barbara
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
Vietnamese - German Centre for Medical Research (VG-CARE), Hanoi, Vietnam.
J Med Virol. 2025 Sep;97(9):e70594. doi: 10.1002/jmv.70594.
The pathogenesis of dengue remains complex and incompletely understood. One proposed mechanism involves the virus evading host immune responses through the upregulation and/or secretion of immune-inhibitory molecules. This study investigates the association between plasma levels of soluble human leukocyte antigen G (sHLA-G), a known immunoregulatory molecule, and dengue severity in hospitalized patients. A total of 238 dengue patients and 118 healthy controls were enrolled. Dengue infection was confirmed by real-time RT-PCR, and patients were clinically categorized as having dengue fever without warning signs (DF), dengue with warning signs (DWS), or severe dengue (SD), according to WHO guidelines. Laboratory parameters were assessed upon hospital admission, and plasma sHLA-G levels were measured using ELISA. sHLA-G levels were significantly elevated in dengue patients compared to healthy controls (median [range]: 42.7 [7.10-1300] U/mL vs. 11.1 [4.7-620] U/mL; p < 0.001). After adjusting for age, sex and disease severity, a significant association was observed between sHLA-G levels and days of illness (β = 0.1, p = 0.03). Patients requiring close medical monitoring (DWS/SD) showed higher sHLA-G levels (51.0 [7.17-525] U/mL) than those having dengue fever without warning signs (38.0 [7.10-1300] U/mL); p = 0.011. While ALT and AST were positively correlated with sHLA-G levels in all patients, total lymphocyte counts were inversely correlated with sHLA-G in severe cases (r = -0.78, p = 0.002). Elevated sHLA-G levels are associated with dengue severity and may serve as a useful marker for identifying high-risk cases and for guiding clinical monitoring. Clinical trial registration: Not applicable.
登革热的发病机制仍然复杂且尚未完全明确。一种提出的机制涉及病毒通过上调和/或分泌免疫抑制分子来逃避宿主免疫反应。本研究调查了可溶性人类白细胞抗原G（sHLA-G，一种已知的免疫调节分子）的血浆水平与住院患者登革热严重程度之间的关联。共纳入了238例登革热患者和118例健康对照。通过实时逆转录聚合酶链反应（RT-PCR）确诊登革热感染，并根据世界卫生组织（WHO）指南将患者临床分类为无警示体征的登革热（DF）、有警示体征的登革热（DWS）或重症登革热（SD）。入院时评估实验室参数，并使用酶联免疫吸附测定（ELISA）法测量血浆sHLA-G水平。与健康对照相比，登革热患者的sHLA-G水平显著升高（中位数[范围]：42.7[7.10 - 1300]U/mL对11.1[4.7 - 620]U/mL；p < 0.001）。在调整年龄、性别和疾病严重程度后，观察到sHLA-G水平与病程天数之间存在显著关联（β = 0.1，p = 0.03）。需要密切医疗监测的患者（DWS/SD）的sHLA-G水平（51.0[7.17 - 525]U/mL）高于无警示体征的登革热患者（38.0[7.10 - 1300]U/mL）；p = 0.011。虽然在所有患者中谷丙转氨酶（ALT）和谷草转氨酶（AST）与sHLA-G水平呈正相关，但在重症病例中总淋巴细胞计数与sHLA-G呈负相关（r = -0.78，p = 0.002）。sHLA-G水平升高与登革热严重程度相关，可能作为识别高危病例和指导临床监测的有用标志物。临床试验注册：不适用。
